. In the yeast S. cerevisiae, growth and cell division are coordinated at a G1-specific state referred to as the """"""""restriction point"""""""" or """"""""Start."""""""" At Start, yeast cells monitor growth and adjust the rate of cell-cycle progression accordingly. Cells exposed to stress also alter cell-cycle progression at G1, although stress induces only transient arrest. In both cases, cell-cycle progression appears to be dependent upon the regulated accumulation of G1-specific cyclins. As cyclin synthesis falls, cell division slows or stops. The cAMP-dependent protein kinase (PKA) pathway appears to regulate cell-cycle progression in response to growth, most likely by regulating protein synthesis of the G1 cyclin, Cln3p. Consistent with this model, PKA activity regulates expression of the ribosome protein genes. The transcription factors Msn2p and Msn4p mediate function of both the PKA pathway and the general stress response. Thus, it will be interesting to determine if Msn2p activation, by PKA depletion or exposure to stress, induces expression of one or more genes that inhibit Cln3p translation. One such candidate gene is the growth inhibitory gene YAK1 that was previously implicated in PKA-dependent growth. If YAK1 has a role in ribosome gene expression of Cln3p synthesis, it will also be important to determine, by genetic or molecular approaches, the specific mechanism by which Yak1p functions. Regardless of whether the specifics of this model are correct, results obtained from studies proposed as part of the objectives should contribute to our understanding of the mechanism by which growth and cell division are coordinately regulated to allow proper entry into G0. Most mammalian cells exist in a quiescent state for prolonged periods, so information gained about the mechanism of this coordination will be generally useful. The observation that PKA and the general stress response share a common transcription factor suggests that PKA plays an important role in adaptation to stress. Thus, our results should also have a direct bearing on studies into the physiological consequences of, and molecular responses to, stress.
